# Dynamic response by commensal E. coli two-component system Cpx contributes to C. elegans development

## TL;DR

This study shows that the E. coli Cpx system dynamically affects C. elegans development and stress tolerance, depending on environmental factors and metabolism.

## Contribution

The study reveals that the dynamic response of the E. coli Cpx system, not just its activation, influences C. elegans development and stress resistance.

## Key findings

- E. coli ΔcpxR delays C. elegans development and activates the mitochondrial unfolded protein response via reactive oxygen species.
- L-histidine-related metabolism in ΔcpxR contributes to developmental delay in LB medium but not in M9 minimal medium.
- N-acetylcysteine concentration shifts the effect of ΔcpxR from developmental delay to survival resistance in C. elegans.

## Abstract

The Caenorhabditis elegans–Escherichia coli system is advantageous for studying host-microbe interactions at the single-gene level. By screening with this system, we identified that the deletion of cpxR, an E. coli transcription factor for the envelope stress response, delays C. elegans development. This finding led us to investigate how this gene regulates host development.

We identified that E. coli ΔcpxR induced C. elegans developmental delay and activated the C. elegans mitochondrial unfolded protein response pathway through reactive oxygen species. It is widely accepted that the Cpx system is important for bacterial pathogenesis, and activating CpxR is regarded as an antimicrobial strategy. Moreover, we discovered that ΔcpxR cultured in LB medium, not cultured in M9 minimal medium, delayed C. elegans development, and the L-histidine-related metabolism of ΔcpxR contributed mostly to the difference. The metabolic fluctuations of commensal bacteria reveal that, rather than the activation of the E. coli Cpx response, the dynamic response of the E. coli Cpx system really contributes to C. elegans development. Furthermore, as the concentration of N-acetylcysteine increased, the phenotype of C. elegans fed ΔcpxR transitioned from developmental delay to survival resistance. The dynamic response is also indicated in the process in which commensal E. coli improves the stress tolerance of the host C. elegans to N-acetylcysteine.

Our results illustrate that environmental factors can shape the regulation of the E. coli Cpx response to C. elegans, providing new evidence for why Cpx-mediated virulence phenotypes are inconsistent among gram-negative species in different ecological niches.

The online version contains supplementary material available at 10.1186/s12915-026-02513-x.